In recent years, attempts have been made to use artificially differentiated pluripotent stem cells for drug discovery screening and regenerative medicine (e.g., Non Patent Literature 1). The pluripotent stem cells described herein refer to cells which have an ability to differentiate into various functional cells. The pluripotent stem cells are caused to differentiate into cells having functions specific to a certain organ or cell type depending on what is the purpose of drug discovery screening or regenerative medicine. For example, iPS cells are used as the pluripotent stem cells. However, in many cases, the artificially differentiated pluripotent stem cells are capable of reproducing only a part of vital functions in vivo. Accordingly, the functions of the artificially differentiated pluripotent stem cells are much lower than the functions of cells in vivo.
In drug discovery screening tests using cells, the cells show drug susceptibility and toxic reaction. It is required to show drug susceptibility and toxic reaction that are similar to those obtained in a test performed in a living body, that is, a so-called in vivo test. The above-mentioned prior art is insufficient for using pluripotent stem cells artificially differentiated for such an application. Therefore, there is a demand for differentiating pluripotent stem cells to more mature cells. The more mature cells described herein refer to cells having functions whose expression level is equivalent to that of functions of cells in vivo.
In the field of conventional medicine, organ transplantation and artificial organ transplantation are carried out. However, there are problems with the transplantations such as shortage of donors and transplant rejection. For example, in clinical practice, organ transplantation and replacement with artificial organs are carried out to treat severe organ failures. However, the organ transplantation and artificial organ transplantation have some fundamental problems that have not been solved. There are problems with organ transplantations such as rejections and critical shortage of donors, and artificial organs are only capable of replacing some of the functions of an organ for a limited period of time (e.g., Patent Literature 1 and 2).
On the other hand, in the field of regenerative medicine, artificial creation of human tissues is carried out. A method is known in which terminally differentiated cells are seeded on a support or scaffolding for this creation. Further, in recent years, a method for preparing a tissue and an organ (Patent Literature 3) and a method for preparing islet cells by inducing undifferentiated cells (Patent Literature 4) have been disclosed.
Patent Literature 3 discloses a method for co-culturing a mesenchymal cell, an organ cell, and a vascular endothelial cell, thereby producing a cell cluster which is called an organ bud. The organ bud grows into an organ and can be transplanted in a living body. An organ bud produced by this method is an extremely favorable implant. On the other hand, there is a risk that when the organ bud is transplanted, a cell in the organ bud may differentiate into a cell of an organ other than the transplantation target (Non Patent Literature 2). A cell of an organ other than the transplantation target refers to a cell other than a cell of the organ into which the organ bud grows. Examples of this cell include a fibrous cell and a bone cell. Accordingly, there is a demand for minimizing the risk that a cell in an organ bud differentiates into a cell of an organ other than the transplantation target.